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Crosstalk Between IGF1R and Estrogen Receptor Signaling in Breast Cancer

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Abstract

After the discovery that depriving certain breast tumors of estrogen promoted tumor regression, therapeutic strategies aimed at depriving tumors of this hormone were developed. The tumorigenic properties of estrogen are regulated through the estrogen receptor-α (ER), making understanding the mechanisms that activate this receptor highly relevant. In addition to estrogen activating the ER, other growth factor pathways, such as the insulin-like growth factors (IGFs), can activate the ER. This review will examine the interaction between these two pathways. Estrogen can activate the growth stimulatory properties of the IGF pathway via ER’s genomic and non-genomic functions. Further, blockade of ER function can inhibit IGF-mediated mitogenesis and blocking IGF action can inhibit estrogen stimulation of breast cancer cells. Collectively, these observations suggest that the two growth regulatory pathways are tightly linked and a more thorough understanding of the mechanism of this crosstalk could lead to improved therapeutic strategies in breast cancer.

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Abbreviations

ER:

estrogen receptor

IGF:

insulin-like growth factor

IGF1R:

type 1 insulin-like growth factor receptor

EGF:

epidermal growth factor

EGFR:

epidermal growth factor receptor

MAPK:

mitogen activated protein kinase

SRC:

steroid receptor co-activator

IRS:

insulin receptor substrate

ERE:

estrogen response element

SERM:

selective estrogen receptor modulator

PI3K:

PI3 kinase

IGFBP:

IGF-binding protein

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Authors and Affiliations

  1. Department of Pharmacology, Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA

    Dedra H. Fagan & Douglas Yee

  2. Department of Medicine, University of Minnesota, Minneapolis, MN, USA

    Douglas Yee

  3. MMC 806, 420 Delaware St. SE, Minneapolis, MN, 55455, USA

    Douglas Yee

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  1. Dedra H. Fagan
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Fagan, D.H., Yee, D. Crosstalk Between IGF1R and Estrogen Receptor Signaling in Breast Cancer. J Mammary Gland Biol Neoplasia 13, 423–429 (2008). https://doi.org/10.1007/s10911-008-9098-0

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